In your work with the Pritzker Neuropsychiatric Research Consortium, have you uncovered any new genes that you think might be related to mental illnesses besides major depression?

Q. In your work with the Pritzker Neuropsychiatric Research Consortium, have you uncovered any new genes that you think might be related to mental illnesses besides major depression?

Answer By: Huda Akil, Ph.D.

Co-Director and Research Professor, The Molecular & Behavioral Neuroscience Institute

Distinguished University Professor and Quarton Professor of Neurosciences

University of Michigan

Yes, the Pritzker Consortium is interested in three severe psychiatric disorders—major depression, bipolar disorder and schizophrenia. We hope to discover the genes involved in these illnesses by studying the genetic variations that are associated with these illnesses and by studying the brains of individuals with these disorders to discover genes and proteins that are altered either because of the original genetics or because of environmental and developmental factors that have converged to change the brain.

The first class of studies relying on genetics is more fruitful in bipolar illness and schizophrenia as these disorders are more clearly heritable. Although, it is also clear that genetics is by no stretch the only determinant, and even identical twins can diverge on whether or not they develop these illnesses. We have learned that many different genes are likely to contribute to these disorders, and genes that are at play in one family may not overlap with genes in another family to produce a similar syndrome. This complexity requires that we gather information from a huge number of individuals who are affected, and the Pritzker Consortium participates in a broader Psychiatric Genomics Consortium where information is pooled and analyzed from tens of thousands of individuals to discover genes that can cause vulnerability to these illnesses.

The other approach of studying postmortem brains relies on the Pritzker Brain Bank. We have samples from individuals who had been diagnosed with bipolar disorder and schizophrenia as well as major depression and people without a mental illness. We have somewhat fewer samples for the first two, since the disorders are rarer than depression. But our studies are teaching us a great deal about the signature of these illnesses on the brain, their similarities as well as their differences. For example, genes related to the circadian clock are altered in bipolar illness, and many genes related to neurotransmitters and to immune function are altered in schizophrenia.

The challenge is to combine the information on genetics and on brain function to define key players that might represent new types of targets for treatment.